Left ventricular end-diastolic pressure as an independent predictor of outcome during balloon aortic valvuloplasty.

OBJECTIVES: In this study, we examined the predictive value of the left ventricular end-diastolic pressure (LVEDP) in patients undergoing balloon aortic valvuloplasty (BAV). BACKGROUND: The LVEDP is a useful indicator of hemodynamic status in patients with severe aortic stenosis. In BAV, decompensated heart failure is associated with worse outcomes. METHODS: We identified all consecutive patients with severe symptomatic aortic stenosis who underwent retrograde BAV at the Massachusetts General Hospital from 2004 to 2008. Patients were stratified and compared according to their baseline LVEDP into ≤15 mm Hg, 16-20 mm Hg, 21-25 mm Hg, and ≥26 mm Hg. Procedural and in-hospital outcomes and adverse events were compared. Multivariate logistic regression was used for the adjusted analysis. RESULTS: A total of 111 patients with a mean age of 83±11 years underwent BAV. Of these, the LVEDP was ≤15 mm Hg in 29 (26%), 16-20 mm Hg in 41 (37%), 21-25 mm Hg in 16 (14%), and ≥26 mm Hg in 25 (23%) patients. Baseline characteristics were similar among the four groups. Noticeably, patients with high LVEDP levels had significantly higher rates of the combined endpoint of in-hospital death, myocardial infarction (MI), cardiopulmonary arrest, and tamponade was P = 0.02. Periprocedural MI was more common among those with higher LVEDP (16% vs. 2.3%; P = 0.04). Multivariate analysis revealed LVEDP (OR 1.08, for each mm Hg increase in pressure, 95 % CI 1.02-1.14), small LV chamber size, and New York Heart Association class as independent predictors of adverse outcomes. CONCLUSIONS: The LVEDP is an important independent predictor of poor in-hospital outcome during BAV. In these patients, the immediate hemodynamic status may be more important than the baseline left ventricular systolic function. Hemodynamic optimization before or during BAV should be considered and may be beneficial.

Patients with small left ventricular size undergoing balloon aortic valvuloplasty have worse intraprocedural outcomes.

OBJECTIVES: To evaluate the impact of left ventricular (LV) chamber size on procedural and hospital outcomes of patients undergoing aortic valvuloplasty. BACKGROUND: Balloon aortic valvuloplasty (BAV) is used as an integral step during transcatheter aortic valve implantation. Patients with small, thickened ventricles are thought to have more complications during and following BAV. METHODS: Retrospective study of consecutive patients with severe, symptomatic calcific aortic stenosis who underwent retrograde BAV at Massachusetts General Hospital. We compared patients with left ventricular end-diastolic diameters (LVEDD) <4.0 cm (n = 31) to those with LVEDD ≥4.0 cm (n = 78). Baseline and procedural characteristics as well as clinical outcomes were compared. Multivariate logistic regression was used for the adjusted analysis. RESULTS: Patients with smaller LV chamber size were mostly women (80.7% vs. 19.4%, P < 0.01) and had a smaller body surface area (BSA), (1.61 ± 0.20 m(2) vs. 1.79 ± 0.25 m(2) , P < 0.01). Patients with smaller LV chamber size had higher ejection fractions and thicker ventricles. Otherwise, baseline characteristics were similar. The intraprocedural composite of death, cardiopulmonary arrest, intubation, hemodynamic collapse, and tamponade was higher for patients with LVEDD < 4.0 cm (32.3% v. 11.5%, P = 0.01). Adjusting for age, gender, BSA, LV pressure, and New York Heart Association class, LVEDD < 4.0 cm remained an independent predictor of procedural (OR 5.1, 95% CI 1.4-18.2) and in-hospital complications (OR 3.8, 95% CI 1.2-11.6). CONCLUSIONS: Compared to patients undergoing BAV with LVEDD ≥4.0 cm, those with smaller LV chambers had worse procedural and in-hospital outcomes.

A Case Report of Pericardial Effusion with False-Positive Mesothelioma and Adenocarcinoma Markers as the Initial Presentation of Systemic Lupus Erythematous.

Pericardial effusion or the accumulation of fluid in the pericardial sac, can result from infectious, malignant, or autoimmune processes such as systemic lupus erythematous (SLE). However, pericardial effusion is infrequently the first presentation of SLE. Here, we describe the case of a 54-year-old African American woman who presented with hypertensive emergency and was found to have pericardial effusion on echocardiogram. Her hypertensive symptoms resolved with medical management and a work up were positive for serum markers of SLE and mesothelioma cell markers (calretinin, CK 5/6) and adenocarcinoma marker MOC31 in the pericardial fluid. Her effusion ultimately improved on high-dose steroid therapy and has not recurred in one year. Given normal pleura and pericardium on computed tomography (CT) imaging and long-term clinical improvement in SLE therapy, we hypothesize that she had false-positive mesothelioma markers in the setting of SLE.

Bioelectrical impedance analysis of body composition and survival in patients with heart failure.

BACKGROUND: Studies have shown that higher body mass index (BMI) is associated with improved prognosis in heart failure (HF), and this is often termed the obesity paradox. HYPOTHESIS: Analysis of body composition may reveal that muscle mass rather than adipose tissue accounts for the obesity paradox. METHODS: Bioelectrical impedance analysis of body composition in 359 outpatients with HF was performed using an In Body 520 body composition scale (Biospace Inc., California). Body fat and lean mass were indexed by height (m2 ). The cohort was stratified by median fat and lean mass indexed by height. RESULTS: The mean age of patients studied was 56 ± 14; mean left ventricular ejection fraction was 38 ± 16%. Patients with higher indexed body fat mass had improved 5-year survival over patients with lower indexed body fat mass (90.2% vs 80.1%, P = 0.008). There was also improved survival in patients with high vs low indexed lean body mass (89.3% vs 80.9%, P = 0.036). On multivariable analysis, higher indexed body fat mass, but not lean body mass, was independently associated with improved survival (HR 0.89, per kg/m2 increase in indexed body fat mass, P = 0.044); however, this was attenuated after adjustment for diabetes. The combination of low lean with low-fat mass was independently associated with poor prognosis. CONCLUSIONS: Our data suggest that higher fat mass-and to a lesser extent higher lean mass-is associated with improved outcomes in HF. Further investigations of specific components of body composition and outcomes in HF are warranted.

Short-term pacing in the mouse alters cardiac expression of connexin43.

BACKGROUND: Cardiac insults such as ischemia, infarction, hypertrophy and dilatation are often accompanied by altered abundance and/or localization of the connexin43 gap junction protein, which may predispose towards arrhythmic complications. Models of chronic dyssynchronous cardiac activation have also been shown to result in redistribution of connexin43 in cardiomyocytes. We hypothesized that alterations in connexin43 expression and localization in the mouse heart might be induced by ventricular pacing over a short period of time. RESULTS: The subdiaphragmatic approach was used to pace a series of wild type mice for six hours before the hearts were removed for analysis. Mice were paced at 10-15% above their average anesthetized sinus rate and monitored to ensure 1:1 capture. Short-term pacing resulted in a significant reduction in connexin43 mRNA abundance, a partial redistribution of connexin43 from the sarcolemma to a non-sarcolemmal fraction, and accumulation of ubiquitinated connexin43 without a significant change in overall connexin43 protein levels. These early pacing-induced changes in connexin43 expression were not accompanied by decreased cardiac function, prolonged refractoriness or increased inducibility into sustained arrhythmias. CONCLUSION: Our data suggest that short-term pacing is associated with incipient changes in the expression of the connexin43 gap junction, possibly including decreased production and a slowed rate of degradation. This murine model may facilitate the study of early molecular changes induced by pacing and may ultimately assist in the development of strategies to prevent gap junction remodeling and the associated arrhythmic complications of cardiac disease.

Obesity and the obesity paradox in heart failure.

Obesity has reached epidemic proportions in the general population and is associated with an increased risk for the development of new-onset heart failure (HF). However, in acute and chronic HF, overweight and mild to moderate obesity is associated with substantially improved survival compared with normal weight. This phenomenon has been termed the "obesity paradox" in HF. The majority of data pertaining to the obesity paradox identifies obesity with body mass index; however, the reliability of this method has been questioned. Newer studies have explored the use of other measures of body fat and body composition, including waist circumference, waist-to-hip ratio, skinfold thickness, and bioelectrical impedance analysis of body composition. The relationship between the obesity paradox and cardiorespiratory fitness in HF is also discussed in this review, and we explore the various potential explanations for the obesity paradox and summarize the current evidence and guidelines for intentional weight loss treatments for HF in the obese population.

Pocket change: a simple educational intervention increases hospitalist documentation of comorbidities and improves hospital quality performance measures.

BACKGROUND: Complete documentation of patient comorbidities in the medical record is important for clinical care, hospital reimbursement, and quality performance measures. We designed a pocket card reminder and brief educational intervention aimed at hospitalists with the goal of improving documentation of 6 common comorbidities present on admission: coagulation abnormalities, metastatic cancer, anemia, fluid and electrolyte abnormalities, malnutrition, and obesity. METHODS: Two internal medicine inpatient teams led by 10 hospitalist physicians at an academic medical center received the educational intervention and pocket card reminder (n = 520 admissions). Two internal medicine teams led by nonhospitalist physicians served as a control group (n = 590 admissions). Levels of documentation of 6 common comorbidities, expected length of stay, and expected mortality were measured at baseline and during the 9-month study period. RESULTS: The intervention was associated with increased documentation of anemia, fluid and electrolyte abnormalities, malnutrition, and obesity in the intervention group, both compared to baseline and compared to the control group during the study period. The expected length of stay increased in the intervention group during the study period. CONCLUSIONS: A simple educational intervention and pocket card reminder were associated with improved documentation and hospital quality measures at an academic medical center.

An optimized and simplified system of mouse embryonic stem cell cardiac differentiation for the assessment of differentiation modifiers.

Generating cardiomyocytes from embryonic stem cells is an important technique for understanding cardiovascular development, the origins of cardiovascular diseases and also for providing potential reagents for cardiac repair. Numerous methods have been published but often are technically challenging, complex, and are not easily adapted to assessment of specific gene contributions to cardiac myocyte differentiation. Here we report the development of an optimized protocol to induce the differentiation of mouse embryonic stem cells to cardiac myocytes that is simplified and easily adapted for genetic studies. Specifically, we made four critical findings that distinguish our protocol: 1) mouse embryonic stem cells cultured in media containing CHIR99021 and PD0325901 to maintain pluripotency will efficiently form embryoid bodies containing precardiac mesoderm when cultured in these factors at a reduced dosage, 2) low serum conditions promote cardiomyocyte differentiation and can be used in place of commercially prepared StemPro nutrient supplement, 3) the Wnt inhibitor Dkk-1 is dispensable for efficient cardiac differentiation and 4) tracking differentiation efficiency may be done with surface expression of PDGFRα alone. In addition, cardiac mesodermal precursors generated by this system can undergo lentiviral infection to manipulate the expression of specific target molecules to assess effects on cardiac myocyte differentiation and maturation. Using this approach, we assessed the effects of CHF1/Hey2 on cardiac myocyte differentiation, using both gain and loss of function. Overexpression of CHF1/Hey2 at the cardiac mesoderm stage had no apparent effect on cardiac differentiation, while knockdown of CHF1/Hey2 resulted in increased expression of atrial natriuretic factor and connexin 43, suggesting an alteration in the phenotype of the cardiomyocytes. In summary we have generated a detailed and simplified protocol for generating cardiomyocytes from mES cells that is optimized for investigating factors that affect cardiac differentiation.

Identification of binding partners for the cytoplasmic loop of connexin43: a novel interaction with ß-tubulin.

Connexin43 (Cx43), a component of gap junctions, has a relatively large carboxy-terminal region with multiple proteomic interactions. Proteomic interactions with its cytoplasmic loop, however, are poorly defined. The goal of this study is to examine proteomic interactions involving the cytoplasmic loop (CL) of Cx43. The authors utilized various techniques, including glutathione-S-transferase (GST) pull-down, immunoblot analysis, two-dimensional (2D) gel electrophoresis, and mass spectrometry, to elucidate binding partners for Cx43-CL. The authors identified novel interactions with Cx43-CL involving α- and ß-tubulin, myelin basic protein, and Purα. Because tubulin interacts with the C-terminus of Cx43 (Cx43-CT), the authors further investigated the nature of the interaction between ß-tubulin and Cx43-CL. ß-Tubulin binds with the full length of Cx43-CL with approximately one-fifth the affinity of the interaction between Cx43-CT and ß-tubulin. This study demonstrates novel proteomic interactions involving Cx43-CL that may lead to a more complete understanding of trafficking and gating of gap junction channels.